Previous papers and patents claimed to be able to detect the differences between normal and abnormal (pre-cancerous and cancerous) cells and tissue by inspection of the infrared spectra of these cells and tissues. Although some of these patent applications and scientific reports present al least partially valid data, the interpretation of these data mostly lacks the specific understanding of the origin of spectral differences between normal and abnormal cells and tissues.
Early patent applications and scientific reports by Wong and coworkers were based on faulty interpretation of spectral differences in cervical and other cells and tissues. These studies failed to take into account the spectral changes in cells and tissues associated with maturation and differentiation of cells. Since certain cancerous and pre-cancerous diseases are accompanied by disruptions of the regular maturation of cells in tissues, some weak correlation between cancerous disease and spectral features was observed. The inconsistencies of the correlations were blamed on failures of standard methods of cytology and pathology.
Although some of the shortcomings of the earlier patents had been established, U.S. Pat. No. 5,733,739 which amplifies the misinterpretations of earlier reports and patents, and uses data that are clearly misinterpreted, has issued. For example, the patent used infrared (IR) spectral data from extracellular materials, such as mucus, and other confounding factors such as blood cells, for the interpretation of the spectral characteristics of cervical cells. Thus, most data used in their patent are unrelated to actual cancerous and pre-cancerous disease but rather to gross spectral changes due to contamination of cervical cells. The actual spectral changes due to cancerous disease, to be discussed below, cannot be detected by the crude methods described in U.S. Pat. No. 5,733,739.
U.S. Pat. No. 5,596,992 uses infrared spectroscopy to distinguish normal from cancerous leukocytes and other cells by multivariate statistical methods. These studies use highly homogeneous samples and, therefore, have a much higher success in predicting disease from infrared data. However, they have failed to realize a source of spectral heterogeneity that confounds the interpretation of the data, and is due to the stages of cells' reproductive cycle.
We have established that identical and highly pure cells still present spectral heterogeneity due to the differences in their development. Only when cells are separated into homogeneous fractions according to their stage in the cell cycle will homogeneous spectral patterns be observed. Under these circumstances, single cells in one given stage exhibit spectral characteristics that can be directly related to the presence of cancer. Thus, the understanding of the cellular biology underlying the cell's reproductive cycle is necessary for a reliable diagnosis of disease. A method will be reported here that allows the detection of single cells that carry the signature of cancerous disease.